Molecular biology, endocrinology, and pharmacology of the cardiac renin-angiotensin system. 1990

K Lindpaintner, and D Ganten
German Institute for High Blood Pressure Research, Heildelberg.

Recent evidence for the existence of extrarenal tissue renin-angiotensin systems has raised the question whether such a system also exists in the heart. In this communication, we present evidence for a cardiac renin-angiotensin system based on molecular biological and biochemical data. In addition, we address the question whether the components of this system interact as a locally integrated, biologically functioning unit. Using radiolabeled cRNA probes prepared from specific cDNA fragments, we were able to document renin and angiotensinogen gene expression in atria and ventricles of the rat heart by Northern blot and liquid hybridization analysis. Relative signal strength for both mRNAs was highest in the atria, followed by the right and left ventricle. Using specific, HPLC-controlled RIAs for angiotensin peptides, we demonstrated the presence of both angiotensin I and angiotensin II in all anatomical regions of the monkey and rat heart. Similarly, the presence of converting enzyme activity was ascertained by direct in vitro determinations. Additional experiments evaluating the spontaneous release of angiotensinogen from isolated, perfused rat hearts revealed a bimodal pattern of high, but rapidly declining rates during the first hour (perhaps representing the washout of a pool sequestered from plasma), followed by a prolonged period of steady, low level release, consistent with the secretion of locally synthesized protein. In separate experiments aimed at examining the possible local integration of the components of the cardiac renin-angiotensin system, we measured angiotensin II concentrations in the coronary sinus effluent of isolated, perfused rat hearts. Infusion of angiotensin I resulted in the prompt appearance of angiotensin II, amounting to a single pass fractional conversion of 6.42 +/- 0.33%.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D012084 Renin-Angiotensin System A BLOOD PRESSURE regulating system of interacting components that include RENIN; ANGIOTENSINOGEN; ANGIOTENSIN CONVERTING ENZYME; ANGIOTENSIN I; ANGIOTENSIN II; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming ANGIOTENSIN I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to ANGIOTENSIN II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal VASCULAR SMOOTH MUSCLE, leading to retention of salt and water in the KIDNEY and increased arterial blood pressure. In addition, angiotensin II stimulates the release of ALDOSTERONE from the ADRENAL CORTEX, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down BRADYKININ, a powerful vasodilator and component of the KALLIKREIN-KININ SYSTEM. Renin-Angiotensin-Aldosterone System,Renin Angiotensin Aldosterone System,Renin Angiotensin System,System, Renin-Angiotensin,System, Renin-Angiotensin-Aldosterone
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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